Causes of ALS

Amyotrophic lateral sclerosis (ALS), also referred to as Lou Gehrig’s disease, is a diverse and mystifying disease. In more than nine out of every 10 cases diagnosed, there’s no clear identifying cause – most patients are without the affected family members that signal an obvious genetic history. 

Also, nothing about the way patients live their lives gives clues to what causes ALS. Nothing, so far, in patients’ diets, where they’ve lived, how they’ve lived or what they’ve done with their lives seems to explain why they’ve developed this late onset, fully developed, progressive disease.

ALS in the Family

 In about 5 percent of cases, a clear genetic history exists. The disease is classed as autosomal dominant in these patients; that is, that almost half of all family members show an undeniable history of ALS.

Studies in the early 1990s on genetic forms of ALS revealed that a single gene defect could account for a portion of these familial cases. Roughly 15 to 20 percent of familial ALS stems from mutations in the gene for the enzymes superoxide dismutase 1 (SOD1) or copper zinc superoxide dismutase.

That means approximately 1 to 2 percent of all cases of ALS stem from SOD mutations. Another 3 percent or so of ALS results from mutations in other genes.

Getting at the Cause of ALS

 Still, for the majority of ALS cases – called sporadic ALS – cause is unknown. Something genetic is almost certainly at work, if only for a predisposition to the disease. And some subtle environmental element is also suspected – a toxin, perhaps.

When a patient gets an ALS diagnosis, the disease has been underway for some time. Once ALS begins, it spreads throughout the central nervous system, both brain and spinal cord.

ALS is basically thought to be an illness of motor neurons. But it’s also one of astrocytes, the common nervous system cells that support motor neurons. Throughout the disease, a number of cell processes go awry, contributing to and maintaining ALS’s progress. So far, no single one of them appears far more important than another.

Packard Center researchers and its affiliated ALS scientists are targeting these pathogenic processes as the best way to understand the cause of ALS and cure it:

• • SOD1 mutations
• • Oxidative damage
• • Aggregated proteins
• • Abnormal mitochondria
• • Growth factor deficiency
• • Cell death pathways
• • Axon transport defects
• • Abnormal astroglia
• • Excitotoxicity
• • TDP-43